Experimental Production and Control of an Abnormality in Acetylcholine Metabolism Present in Epileptogenic Cortex

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Abstract
In a previous work (Jour. Appl. Physiol. 4: 669. 1952) it was reported that slices of human focal epileptogenic cerebral cortex show a failure to produce bound acetylcholine (ACh) when incubated in vitro. A similar defect in ACh metabolism has now been found in cerebral cortex from animals with convulsions induced by treatment with methionine sulfoximine, and in normal cortical tissue when incubated under reduced O2 tension. In all 3 conditions the production of free ACh during incubation was normal. Treatment of animals with anesthetics or certain anti-convulsant drugs increased the subsequent production of bound ACh by excised cerebral cortex and overcame the depression of bound ACh found with tissue from methionine sulfoximine-treated animals or with tissue incubated under reduced O2 tension. Further, the defect in production of bound ACh in human epileptogenic cortex was not found if the tissue was excised after admn. of general anesthesia. The effect of the drug was not removed by rinsing the tissue. The presence in the incubation medium of glutamine or asparagine, but not of glutamic acid, restored to normal the production of bound ACh by human focal epileptogenic cortex, by cortex from methionine sulfoximine-treated animals and by normal cortex incubated under reduced O2 tension. Half-max. effect was obtained with about 1 mM of either substance. Dl-glutamine, L-glutamine and L-asparagine appeared equally effective at equimolar concns. Methionine in the medium reversed the defect in tissue from methionine sulfoximine-treated animals but not in the other 2 cases. None of these substances had any effect on the ACh metabolism of fully oxygenated normal tissue. The mechanism of these effects is discussed.